The Hereditary PalmoplantarKeratodermasBy HAKEEM SAM, M.D. AND DENIS SASSEVILLE, M.D., FRCPC

The palmoplantar keratodermas (PPK) consist of a heterogeneous group of disorderswith overlapping clinical features. The group is distinguished from others by a thickening orhyperkeratosis of the palmar and plantar skin with or without associated features. Recentadvances in molecular genetics and the identification of causative mutant genes have had amajor impact on our understanding of this intriguing group of disorders. PPKs may be hered-itary or acquired, and this issue of Dermatology Rounds reviews the hereditary conditionswith a presentation of their clinical features and the molecular mechanisms of the diseaseprocess.

Clinical features

In 1880, Thost described the first case of diffuse hereditary PPK, which he considered aform of ichthyosis.1 Three years later, Unna clearly separated this entity from the variousichthyoses. In this condition, affected palmoplantar skin often exhibits yellowish waxy areas ofhyperkeratosis surrounded by an erythematous halo.2 In time, additional entities weredescribed, giving rise to the clinical classification of PPK as diffuse, focal, or punctate (Table 1).3,4

Another useful feature is whether the keratoderma is limited to the volar surface of thepalms of the hands and soles of the feet or extends onto the dorsal aspect as well. The termtransgrediens refers to extension of keratosis beyond the volar margins of the palmoplantarskin and progrediens refers to progressive extension beyond the dorsal surfaces.5

Diffuse PPK is further divided into 3 forms. Type I, or classical Vrner type, consists of epidermolytic PPK. Type II, or Unna-Thost type, consists of non-epidermolytic PPK. Type III, in which the hyperkeratotic plaques are not exclusively confined to the palms

and soles, comprises such entities as erythrokeratoderma variabilis of Mendes da Costa orkeratosis palmoplantaris transgrediens et progrediens, Greithers type.3

PPKs are further distinguished by their mode of inheritance and by the presence or absenceof associated features. These may include hyperhidrosis, exacerbation of hyperkeratosis bymanual labour, nail changes, frequent dermatophyte infections, and severe malodor.6,7

PPK and cardiovascular disease

Any patient presenting with PPK and woolly hair should raise suspicions of cardiovasculardisease.5 Naxos disease, named after the Greek island of Naxos, where the disease was firstdescribed by Protonotarios et al, in 1986, is an autosomal recessive diffuse non-epidermolytickeratoderma. Patients have woolly scalp hair at birth, but do not develop potentially fatalcardiac arrhythmia until puberty.8 Dilated cardiomyopathy was a feature of the autosomalrecessive striate epidermolytic keratoderma seen in 3 families from Ecuador and the affectedpatients also had woolly hair.9

Members of theDivision of Dermatology

Denis Sasseville, MD, DirectorEditor, Dermatology Rounds

Alfred Balbul, MD

Alain Brassard, MD

Judith Cameron, MD

Wayne D. Carey, MD

Ari Demirjian, MD

Anna Doellinger, MD

John D. Elie, MD

Odette Fournier-Blake, MD

Roy R. Forsey, MD

William Gerstein, MD

David Gratton, MD

Raynald Molinari, MD

Brenda Moroz, MD

Khue Huu Nguyen, MD

Elizabeth A. OBrien, MD

Maria Rozenfeld, MD

Wendy R. Sissons, MD

Marie St-Jacques, MD

Beatrice Wang, MD

Ralph D. Wilkinson, MD

McGill University Health CentreDivision of DermatologyRoyal Victoria Hospital687 Pine Avenue WestRoom A 4.17Montreal, Quebec H3A 1A1Tel.: (514) 934-1934, local 34648Fax: (514) 843-1570

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In contrast, autosomal dominant striate PPK is notassociated with woolly hair or cardiovascular disease.This is a distinct group of PPK patients with characteris-tic linear hyperkeratosis of the palms extending alongeach finger. There are 2 forms: type 1 or Brnauer-Fuhs-Siemens syndrome (PPKS1) and a second form(PPKS2).10,11 Recently, a form of congenital, diffuse PPKassociated with a total anomalous venous connectionwas reported in a 14-month-old boy.12

PPK and periodontal disease

Papillon-Lefvre syndrome (PLS), initially describedin 1924, is a diffuse transgredient form of PPK thatreveals a strong association with periodontal disease. Age

of onset for hyperkeratosis is around 2-4 years. The onsetof palmoplantar keratoses heralds recurrent periodonti-tis resulting in the loss of all deciduous teeth by 4 years-of-age, and of most secondary teeth by age 14. There is arelatively high incidence of pyogenic liver abscess amongpatients with PLS.13

Interestingly, in 1965, a syndrome bearing a greatresemblance to PLS was described by Haim and Munk.14

Affected patients showed, in addition to congenitalpalmoplantar keratoderma and progressive periodontaldisease, pes planus, recurrent pyogenic infections,arachnodactyly, and a unique tapering of phalanges witha claw-like volar curve. Compared with Papillon-Lefvresyndrome, patients with Haim-Munk syndrome exhibitless periodontal disease, but more severe skin manifesta-tions with a later onset.

Mutilating PPK

First described by H. C. Olmsted in 1927, Olmstedsyndrome consists of a diffuse transgredient symmetricPPK and periorificial keratotic plaques.15 Other impor-tant cutaneous features include mutilating contractures,constricting bands around the fingers leading to auto-amputation (pseudoainhum), follicular keratosis, oralleukokeratosis, dystrophic nails, and diffuse alopecia.Onset is usually in childhood and non-cutaneous fea-tures such as large-joint laxity, absent premolar teeth,and hearing loss for high frequencies may be present.16

Another mutilating PPK is Vohwinkel syndrome.This autosomal dominant disorder is characterized bydiffuse PPK and starfish-shaped hyperkeratotic plaqueson the extensor surfaces of the knuckles, knees, andelbows, pseudoainhum, and sensorineural deafness.17-19

Interestingly, the Bart-Pumphrey syndrome is also asso-ciated with deafness. The cutaneous manifestations ofthe syndrome resemble those of Vohwinkel except thatthe keratoderma is not uniform, but presents with acobblestone aspect, sparing islands of skin and with char-acteristic knuckle pads.3

Loricrin keratoderma is a form of PPK characterizedby a patterned or honeycombed appearance of kerato-derma and mutilating pseudoainhum resemblingVohwinkel syndrome. Although initially thought to be avariant of Vohwinkel syndrome, loricrin keratoderma isnow recognized as a distinct syndrome of PPK withpseudoainhum and ichthyosis.20 Affected patients maypresent as a collodion baby and later develop a general-ized non-bullous congenital ichthyosiform erythro-keratoderma. The PPK seen in these patients is well-demarcated, diffuse, and symmetrically involves thepalms and soles. Unlike Vohwinkel syndrome, ichthyosis,not deafness, is present in loricrin keratoderma.21

Mal de Meleda, or keratosis palmoplantaris transgre-diens of Siemens, is an autosomal recessive PPK withonset shortly after birth. It is named after the Island ofMljet (formerly Meleda) in Croatia, where Bonsnjakovic

Table 1: Clinical features and classification of PPK3,5

Type PPK INH. Characteristic Associations

Diffuse Vrners type AD Epidermolytic No malignancyUnna-Thost AD Non- No malignancytype epidermolyticGreithers type AD Transgredient No malignancyVohwinkels AD Star-fish Deafness,

hyperkeratosis, no malignancymutilating

Loricrin Mutilating IchthyosiskeratodermaBart-Pumphrey AD Knuckle pads Deafness,

no malignancyHuriez AD Sclerodactyly SCC of palms syndrome and soles Clouston AD Alopecia, French-Canadian

nail changes ancestoryNaxos disease AR Woolly hair, Cardiac

NEPPK arrhythmiaPapillon-Lefvre AR Periodontitis No malignancyHaim-Munk AD Less periodonditis,

arachnodactylyMal de Meleda AR, Glove and No malignancy

AD stocking PPK Olmsted ?AD Periorificial No malignancy

plaques, mutilatingFocal Striate PPK with AR Linear No malignancy

woolly hair and hyperkeratosiscardiomyopathy Epidermolytic PPKStriate PPK AD Linear No malignancy(Brnauer-Fuhs- hyperkeratosisSiemens type)Howel-Evans Oral leukokeratosis, SCC of

keratosis pilaris esophagusRichner Hanhart AR Tyrosinemia, No malignancy

corneal ulceration,mental retardation

Pachyonychia AD More severe No malignancyCongenita type1 keratodermaPachyonychia AD Steatocystoma No malignancyCongenita type2 multiplex, vellus

hair cysts, natal teethPunctate Buschke-Fischer- AD No keratotic pits Malignancy

Brauer on creasesPunctate, with Blacks No malignancykeratotic pits on creases

INH., Inheritance; AD, autosomal dominant; AR, autosomal recessive; PPK, palmo-plantar keratoderma; NEPPK, non-epidermolytic palmo-plantar keratoderma; SCC,Squamous cell carcinoma

described the first cases in 1938. Glove-and-stockingtype of PPK is characteristic, along with hyperhidrosis,malodor, and conical tapering of the fingertips that maylead to disabling contracture of the fingers. There mayalso be constricting bands around the digits, perioralerythema, and keratotic plaques over the articulations.7

PPK and thick nails

Hypertrophic nail dystrophy is the most obviousphenotype of the autosomal dominant PPK calledpachyonychia congenita (PC). The Jadassohn-Lewan-dowsky form or type 1 is characterized by doorwedge distal subungual hyperkeratosis, focal palmo-plantar keratoderma and hyperkeratosis of the lingualand/or buccal mucosae. The Jackson-Lawler form ortype 2 has a mild PPK, nail dystrophy, and multiplepilosebaceous cysts, with the possible presence ofabnormal deciduous teeth at birth, pili torti, andhoarseness.22

Hydrotic ectodermal dysplasia or Cloustons syn-drome is a diffuse PPK associated with diffuse hypo-trichosis, alopecia (can be very severe), and mildlythickened to severely dystrophic nails. A characteristicpebbling of the fingertips and periungual skin is pre-sent. The function of the sweat glands is preserved. Thiscondition is most common in patients of French-Cana-dian ancestry and the mode of inheritance is autosomaldominant.5,23

PPK and malignancy

A punctate form of hereditary PPK that may beassociated with an increased risk of malignancy is theBuschke-Fischer-Brauer syndrome.3,24 This syndrome is a rare, autosomal dominant genodermatosis in whichpunctate palmoplantar keratoses develop at ages 12-30.In contrast, a unique form of punctate keratoses of thepalms and soles in conjunction with keratotic pits of thepalmar creases is predominantly seen in blacks and is notassociated with malignancy.25

Howel-Evans syndrome, or tylosis-esophageal cancersyndrome, is a familial form of focal PPK associated witha high incidence of esophageal carcinoma.26 Tylosisrefers to the particular type of focal hyperkeratosis thatis seen in affected family members. The keratotic regionsappear to be predominantly limited to pressure-bearingareas of the palms and soles and exacerbated by manuallabour. Hyperkeratosis develops at the ages of 7-8 yearsand affected family members develop squamous cellcarcinoma of the esophagus 30-40 years later. There is ahigh incidence of oral hyperkeratosis, keratosis pilaris,and xerosis in affected members.3

Diffuse forms of PPK may also be associated with anincreased risk for malignancy. Huriez syndrome is adiffuse form of PPK with sclerodactyly that develops ininfancy. Patients develop squamous cell carcinomas onthe palms and soles.24,27

PPK and metabolic defects

Richner-Hanhart syndrome or tyrosinemia type II isa focal PPK associated with progressive mental retarda-tion and corneal ulcerations. Richner, a Swiss ophthal-mologist, first reported it in 1938, followed by Hanhart,a Swiss geneticist, in 1947. It is caused by a deficiency inthe cytosolic hepatic enzyme tyrosine aminotransferase(TAT).28

Molecular mechanisms of PPK

Mutations underlying the PPK phenotype affect thefollowing proteins (Table 2):

Structural, mainly keratins and loricrin Desmosomal Gap junction component Enzymatic Secreted Mitochondrial Coordinated function of these proteins is required

for the terminal differentiation of keratinocytes andformation of the cornified cell envelope.23

Structural proteins

KeratinsKeratins are intermediate filament proteins that

play a major role in the cytoskeletal framework of

Table 2: Classification of PPK by moleculardefects3-5

Mutated Protein PPK Specific DefectKeratins Epidermolytic and K1 and K9

non-epidermolytic PPKPachyonychia Congenita K6a/K16type 1Pachyonychia Congenita K6b/K17type 2

Loricrin VohwinkelLoricrin keratoderma

Desmosomal Striate PPKS 1 Desmoglein 1Striate PPKS 2 DesmoplakinStriate EPPK, woolly hair Desmoplakinand dilated cardiomyopathyNaxos disease, NEPPK, Plakoglobinwoolly hair, arrythmiaHowel-Evans

Gap Junction Vohwinkel Connexin 26Clouston syndrome Connexin 30Erythrokeratoderma variabilis Connexin 31

Enzymatic Papillon-Lefvre Cathepsin CHaim-Munk syndrome Cathepsin CRichner-Hanhart Hepatic tyrosine

aminotransferase(TAT)

Secreted Mal de Meleda SLURP-1Mitochondria Familial PPK and deafness Mitochondrial

(Bart-Pumphrey) serine tRNA

K, keratin; PPK, palmoplantar keratoderma; PPKS, striate palmo-plantar keratoderma;EPPK, epidermolytic palmo-plantar keratoderma; NEPPK, non-epidermolytic palmo-plantar keratoderma; SLURP-1, secreted mammalian Ly-6/uPAR- related protein 1.

mammalian epithelial cells. Two main types of ker-atin proteins, acidic or type I, and basic or type II,together form an obligate heterodimer. Keratin geneexpression is both tissue-specific and differentia-tion-specific. For example, basal keratinocytes pre-dominantly express the keratin pair K14 and K5.On the other hand, suprabasal cells preferentiallyexpress K1 and K10. Keratin K9 expression isrestricted to the epithelia of the palm and sole.22

As would be expected, mutations in keratin 9gene result in epidermolytic non-transgredient kera-toderma that is limited entirely to the palms andsoles.4 Traditionally, the Unna-Thost and Vrnertypes of diffuse PPK, although clinically indistin-guishable, were separated based on histologic crite-ria of epidermolytic hyperkeratosis. However, bothconditions are caused by mutations affecting thesame segment of keratin 9, suggesting that they mayin fact, be identical.29

In pachyonychia congenita, mutations in keratingene pair K6a and K16 underlie PC type 1, whereasPC type 2 is caused by mutations in K6b and K17.22

Loricrin

Mutations in the loricrin gene lead to loricrinkeratoderma and the Vohwinkel syndrome. Loricrinis a major protein component of the cornified cellenvelope, making up more than 70% of its mass.20,21,30

Desmosomal proteins

Desmosomes play a crucial role in cell-celladhesion. The intracellular portion of desmosomesincludes desmoplakin and plakoglobin. The trans-membrane portion includes the cadherin family ofproteins, eg, desmogleins and desmocollins. Severaldesmosomal protein gene mutations result inunique PPK phenotypes. Desmoglein 1 gene muta-tion underlies the striate keratoderma (PPKS1)whereas desmoplakin gene mutation causesPPKS2.10,11 Both plakoglobin and desmoplakin genemutations have been implicated in Naxos disease.9,31

Finally, desmosomal protein mutations may alsounderlie the Howel-Evans syndrome.23,32

Gap junction proteins

Connexins are the major protein component ofgap junctions.33 The diseases caused by gap junctiongene mutations include Vohwinkels syndrome,erythrokeratoderma variabilis, and Cloustons syn-drome. Vohwinkels disease is caused by mutationsof the gene encoding connexin 26, a proteinexpressed predominantly in cochlear cells.The tissue-specific expression of this protein explains the hear-ing loss associated with this syndrome. Mutations in connexins 31 and 30 have been identified in

patients with erythrokeratoderma variabilis andClouston syndrome, respectively.23,33

Enzymatic protein defects

Cathepsin C is a lysosomal enzyme that may beimportant in activation of serine proteases ininflammatory cells. Cathepsin C gene mutations areresponsible for the classic Papillon-Lefvre syn-drome, as well as its allelic variant, the Haim-Munksyndrome.34,35

Enzymatic defects also characterize the Richner-Hanhart syndrome. Mutations in the gene encodinghepatic tyrosine aminotransferase (TAT) have beenidentified.28

Secreted proteins

Mal de Meleda is caused by mutations inSLURP-1.36,37 The acronym SLURP-1 stands forsecreted mammalian Ly-6/uPAR-related protein 1.The Ly6/uPAR represents a superfamily of secretedproteins with significant homology to snake and frogcytotoxins. The exact role of SLURP-1 is unknown.

Mitochondrial proteins

Mutations in the mitochondrial gene encodingmitochondrial serine transfer RNA (tRNA) may beassociated with a familial form of PPK and deaf-ness.23

Diagnosis

Diagnosis of PPK depends mainly on history,clinical findings, and appropriate histologic or meta-bolic data. The most common findings on biopsy areimpressive hyperkeratosis, acanthosis, and hyper-granulosis.5 Some forms of PPK exhibit prominentepidermolytic hyperkeratosis, characterized by pro-nounced vacuolization of the keratinocytes of themiddle and upper portions of the epidermis. Thisphenomenon is not specific and is also seen in bul-lous congenital ichthyosiform erythroderma, linearepidermal naevus, and various unrelated conditions.

Differential diagnosis

Common causes of acquired hyperkeratosis ofthe palms and soles include calluses, corns, warts,psoriasis, chronic eczematous dermatitis, and kera-toderma climactericum. Less common conditionsinclude lichen planus, pityriasis rubra pilaris,Reiters disease, and arsenical keratoses. Of note,acquired diffuse PPK may be a paraneoplastic mark-er of internal disease. Examples include tripe palms,a form of acquired diffuse, velvety palmar kerato-derma in the setting of acanthosis nigricans andBazexs syndrome (acrokeratosis paraneoplastica),an acquired diffuse acrokeratosis.5,38

TDERMATOLOGYRounds

Management

The clinicians index of suspicion for particularsyndromes or associations should direct the investi-gations. Specific investigations may include skinbiopsy, serum and urine tyrosine levels, liver func-tion tests, and ophthalmologic exams for Richner-Hanhart syndrome.

Medical treatment of PPK may be topical orsystemic. Topical keratolytic agents include 5%-40%salicylic acid in petrolatum or urea, 50% propyleneglycol in water under plastic occlusion, and lacticacid or urea-containing lotions.5 Systemic retinoidshave been effectively used in many cases, includingPapillon-Lefvre syndrome, Vohwinkel syndrome,Mal de Meleda, and Unna-Thost PPK.13,39-41 Whenepidermolytic hyperkeratosis is present, systemicretinoids should be used with caution, as they maycause desquamation of the whole epidermis andpainful erosions. Dermatophyte infections can bemanaged with topical or systemic antifungals, asneeded.6,13 A low phenylalanine diet led to a signifi-cant improvement in skin hyperkeratosis in Richn-er-Hanhart syndrome.28 Focal or punctate plaquesmay be effectively managed by mechanical debride-ment with a blade.5

Conclusions

Earlier descriptions and classifications of heredi-tary PPK were based solely on morphologic and his-tologic criteria. However, many of the molecularmechanisms underlying these disorders have beenrecently worked out. This knowledge should help inthe development of novel therapies.

References1. Thost A. ber erbliche ichthyosis palmaris et plantaris cornea.

(Med. Diss). Horning J, ed. Heidelberg ; 1880.2. Sehgal VN, Kumar S, Narayan S. Hereditary palmoplantar ker-

atoderma (four cases in three generations). Int J Dermatol2001; 40:130-2.

3. Stevens HP, Kelsell DP, Bryant SP, et al. Linkage of an American pedigree with palmoplantar keratoderma andmalignancy (palmoplantar ectodermal dysplasia type III) to17q24. Literature survey and proposed updated classificationof the keratodermas. Arch Dermatol 1996;132:640-51.

4. Rugg EL, Common JE, Wilgoss A, et al. Diagnosis and confir-mation of epidermolytic palmoplantar keratoderma by theidentification of mutations in keratin 9 using denaturing high-performance liquid chromatography. Br J Dermatol 2002;146:952-7.

5. Krol AL. Keratodermas. In: Bolognia JL, Jorizzo JL, Rapini,et al, Eds. Dermatology 1st Ed. Toronto: Mosby; 2003:809-21.

6. Elmros T, Liden S. Hereditary palmo-plantar keratoderma:incidence of dermatophyte infections and the results of topi-cal treatment with retinoic acid. Acta Derm Venereol 1981;61:453-5.

7. Lestringant GG, Hadi SM, Qayed KI, et al. Mal de Meleda:recessive transgressive palmoplantar keratoderma with threeunusual facultative features. Dermatology 1992;184:78-82.

8. Coonar AS, Protonotarios N, Tsatsopoulou A, et al. Gene forarrhythmogenic right ventricular cardiomyopathy with dif-fuse nonepidermolytic palmoplantar keratoderma and woollyhair (Naxos disease) maps to 17q21. Circulation 1998;97:2049-58.

9. Norgett EE, Hatsell SJ, Carvajal-Huerta L, et al. Recessivemutation in desmoplakin disrupts desmoplakin-intermediatefilament interactions and causes dilated cardiomyopathy,woolly hair, and keratoderma. Hum Mol Genet 2000;9:2761-6.

10. Kljuic A, Gilead L, Martinez-Mir A, et al. A nonsense muta-tion in the desmoglein 1 gene underlies striate keratoderma 1.Exp Dermatol 2003;12:523-7.

11. Whittock NV, Ashton GH, Dopping-Hepenstal PJ, et al. Stri-ate palmoplantar keratoderma resulting from desmoplakinhaploinsufficiency. J Invest Dermatol 1999;113:940-6.

12. Hoeger PH, Yates RW, Harper JI. Palmoplantar keratodermaassociated with congenital heart disease. Br J Dermatol1998;138: 506-9.

13. Almuneef M, Al Khenaizan S, Al Ajaji S, et al. Pyogenic liverabscess and Papillon-Lefvre syndrome: not a rare association.Pediatrics 2003;111:e85-e88.

14. Haim S, Munk J. Keratosis palmo-plantaris congenita, witharachnodactyly and a peculiar deformity of the terminalphalanges. Br J Dermatol 1965;77:42-54.

15. Olmsted HC. Keratodermia palmaris et plantaris congenitalis:report of a case showing associated lesions of unusual loca-tions. Am J Dis Child 1927:757-64.

16. Bergonse FN, Rabello SM, Barreto RL, et al. Olmstedsyndrome: the clinical spectrum of mutilating palmoplantarkeratoderma. Pediatr Dermatol 2003;20:323-6.

17. Bell M, Hoede N, Schopf RE. [Pseudo-ainhum in Vohwinkeldisease. Keratoma hereditarium mutilans]. Hautarzt 1993;44:738-41.

18. Camisa C. Keratoderma hereditaria mutilans or Vohwinkelssyndrome. J Am Acad Dermatol 1986;14:512-4.

19. Solis RR, Diven DG, Trizna Z. Vohwinkels syndrome in threegenerations. J Am Acad Dermatol 2001;44:376-8.

20. Matsumoto K, Muto M, Seki S, et al. Loricrin keratoderma:a cause of congenital ichthyosiform erythroderma and collo-dion baby. Br J Dermatol 2001;145:657-60.

21. Maestrini E, Monaco AP, McGrath JA, et al.A molecular defectin loricrin, the major component of the cornified cell envelope,underlies Vohwinkel's syndrome. Nat Genet 1996; 13:70-7.

22. McLean WH. Genetic disorders of palm skin and nail. J Anat2003;202:133-41.

23. Kimyai-Asadi A, Kotcher LB, Jih MH. The molecular basis ofhereditary palmoplantar keratodermas. J Am Acad Dermatol2002;47:327-43.

24. Stevens HP, Kelsell DP, Leigh IM, et al. Punctate palmoplan-tar keratoderma and malignancy in a four-generation family.Br J Dermatol 1996;134:720-6.

25. Rustad OJ, Vance JC. Punctate keratoses of the palms andsoles and keratotic pits of the palmar creases. J Am AcadDermatol 1990;22:468-76.

26. Howel-Evans W, McConnell RB, Clarke CA, et al. Carcinomaof the oesophagus with keratosis palmaris et plantaris (tylo-sis): a study of two families. Q J Med 1958;27:413-29.

27. Lee YA, Stevens HP, Delaporte E, et al. A gene for an autoso-mal dominant scleroatrophic syndrome predisposing to skincancer (Huriez syndrome) maps to chromosome 4q23. Am JHum Genet 2000;66:326-30.

28. Tallab TM. Richner-Hanhart syndrome: importance of earlydiagnosis and early intervention. J Am Acad Dermatol1996;35:857-9.

29. Kuster W, Reis A, Hennies HC. Epidermolytic palmoplantarkeratoderma of Vrner: re-evaluation of Vrners originalfamily and identification of a novel keratin 9 mutation. ArchDermatol Res 2002;294:268-72.

30. Smith F. The molecular genetics of keratin disorders. Am JClin Dermatol 2003;4:347-64.

31. McKoy G, Protonotarios N, Crosby A, et al. Identification of adeletion in plakoglobin in arrhythmogenic right ventricularcardiomyopathy with palmoplantar keratoderma and woollyhair (Naxos disease). Lancet 2000;355:2119-24.

32. McGrath JA. Hereditary diseases of desmosomes. J DermatolSci 1999;20:85-91.

33. Richard G. Connexins: a connection with the skin. ExpDermatol 2000;9:77-96.

TDERMATOLOGYRounds

34. Hart PS, Zhang Y, Firatli E, et al. Identification of cathepsin C muta-tions in ethnically diverse Papillon-Lefvre syndrome patients.J Med Genet 2000;37:927-32.

35. Hart TC, Hart PS, Michalec MD, et al. Haim-Munk syndrome andPapillon-Lefvre syndrome are allelic mutations in cathepsin C.J Med Genet 2000;37:88-94.

36. Eckl KM, Stevens HP, Lestringant GG, et al. Mal de Meleda (MDM)caused by mutations in the gene for SLURP-1 in patients fromGermany, Turkey, Palestine, and the United Arab Emirates. HumGenet 2003; 112:50-6.

37. Fischer J, Bouadjar B, Heilig R, et al. Mutations in the gene encodingSLURP-1 in Mal de Meleda. Hum Mol Genet 2001;10:875-80.

38. Bolognia JL, Brewer YP, Cooper DL. Bazex syndrome (acrokeratosis paraneoplastica). An analytic review. Medicine (Baltimore) 1991;70:269-80.

39. Pacheco JJ, Coelho C, Salazar F, et al. Treatment of Papillon-Lefvresyndrome periodontitis. J Clin Periodontol 2002;29:370-4.

40. Camisa C, Rossana C. Variant of keratoderma hereditaria mutilans(Vohwinkels syndrome). Treatment with orally administeredisotretinoin. Arch Dermatol 1984;120:1323-8.

41. Chang Sing Pang AF, Oranje AP, Vuzevki VD, et al. Successful treat-ment of keratoderma hereditaria mutilans with an aromaticretinoid. Arch Dermatol 1981;117:225-8.

Abstracts of InterestA nonsense mutation in the desmoglein 1 gene underliesstriate keratoderma.KLJUIC A, GILEAD L, MARTINEZ-MIR A, FRANK J,CHRISTIANO AM, ZLOTOGORSKI A.NEW YORK, NYStriate keratodermas (PPKS) (OMIM 148700) are a rare group ofautosomal dominant genodermatoses characterized by palmo-plantar keratoderma typified by streaking hyperkeratosis along eachfinger and extending onto the palm of the hand. We report a four-generation kindred originating from Iran-Syria in which three mem-bers were affected with PPKS. Clinically, these patients present withhyperkeratotic palms and plantar plaques. Direct DNA sequencinganalysis revealed a heterozygous C-to-A transversion at nt 395 ofthe DSG1 gene. This mutation converted a serine residue (TCA) inexon 5 to a nonsense mutation (TAA) designated S132X. Themutation identified in this study is a novel mutation in the DSG1gene and extends the body of evidence implicating the desmogleingene family in the pathogenesis of human skin disorders.Exp Dermatol 2003;12(4):523-7.

Epidermolytic palmoplantar keratoderma of Vorner: re-evaluation of Vorner's original family and identifica-tion of a novel keratin 9 mutation.KUSTER W, REIS A, HENNIES HC.BAD SALZSCHLIRF, GERMANYIn 1901, Hans Vorner observed a family with a diffuse non-transgre-dient palmoplantar keratoderma of autosomal dominant inheritance.Histopathologically, he found epidermolytic hyperkeratosis as acharacteristic sign and diagnostic criterion of this disorder. We per-formed a follow-up study of the family originally seen by Vorner in1901 with clinical, histopathological, and molecular investigations.Clinically, affected family members showed the typical diffuse ker-atoses over the entire surface of the palms and soles sharply borderedby red margins. A mycotic infection was additionally found in twopatients examined. Histopathological investigations confirmed epi-dermolytic hyperkeratosis. Molecular studies revealed a novel muta-tion in keratin 9, N160I, in patients from the family. The mutation in

the coil-1A domain is thought to have a dominant negative effect onthe assembly of keratin intermediate filaments, explaining the domi-nant inheritance of the phenotype. These findings give further evi-dence that palmoplantar keratoderma of Vorner represents the sameentity as palmoplantar keratoderma of Thost, which was recently re-evaluated in Thosts original family and shown to be caused by asimilar mutation, R162 W, in the same segment of keratin 9.Arch Dermatol Res 2002;294(6):268-72.

Upcoming Scientific Meetings5 February 2004American Contact Dermatitis Society15th Annual MeetingRenaissance Hotel, Washington, DCCONTACT: ACDS Office

Tel.: 312-988-7700 Fax: 312-988-7759E-mail: info@contactderm.orgWebsite: www.contactderm.org

6-11 February 200462nd Annual Meeting of the American Academy of DermatologyWashington D.C.CONTACT: Tel.: 1-847-330-0230

Website: www.aad.org

12-15 February 2004The 2004 South Beach SymposiumFlorida Society of Dermatology & Dermatologic SurgeryMiami Beach, FloridaCONTACT: Tel.: 850-5318373

Fax: 850-531-8344Website: www.fsdds.org/meetings.html

31 March - 4 April24th AnnualMeeting of the American Society for Laser Medicine and SurgeryDallas, TexasCONTACT: Tel.: 715-845-9283

Fax: 715-848-2493Email: information@as/ms.org

16-18 April 2004Atlantic Dermatological ConferenceBoston, MassachusettsCONTACT: Tel.: 847-240-1477

Fax: 847-330-1090Email: dcarlson@aad.org

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2003 Division of Dermatology, McGill University Health Centre, Montreal, which is solely responsible for the contents. The opinions expressed in this publication do notnecessarily reflect those of the publisher or sponsor, but rather are those of the authoring institution based on the available scientific literature. Publisher: SNELL MedicalCommunication Inc. in cooperation with the Division of Dermatology, McGill University Health Centre. Dermatology Rounds is a Trade Mark of SNELL Medical CommunicationInc. All rights reserved. The administration of any therapies discussed or referred to in Dermatology Rounds should always be consistent with the recognized prescribing informationin Canada. SNELL Medical Communication Inc. is committed to the development of superior Continuing Medical Education.

This publication is made possible by an educational grant from

Novartis Pharmaceuticals Canada Inc.

S N E L L

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